WO2006109183A1 - Injectable depot formulations and methods for providing sustained release of nanoparticle compositions - Google Patents
Injectable depot formulations and methods for providing sustained release of nanoparticle compositions Download PDFInfo
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- WO2006109183A1 WO2006109183A1 PCT/IB2006/001094 IB2006001094W WO2006109183A1 WO 2006109183 A1 WO2006109183 A1 WO 2006109183A1 IB 2006001094 W IB2006001094 W IB 2006001094W WO 2006109183 A1 WO2006109183 A1 WO 2006109183A1
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- Prior art keywords
- formulation
- surface stabilizer
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- SBWGZAXBCCNRTM-CTHBEMJXSA-N n-methyl-n-[(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl]octanamide Chemical compound CCCCCCCC(=O)N(C)C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO SBWGZAXBCCNRTM-CTHBEMJXSA-N 0.000 description 1
- HEGSGKPQLMEBJL-UHFFFAOYSA-N n-octyl beta-D-glucopyranoside Natural products CCCCCCCCOC1OC(CO)C(O)C(O)C1O HEGSGKPQLMEBJL-UHFFFAOYSA-N 0.000 description 1
- CGVLVOOFCGWBCS-RGDJUOJXSA-N n-octyl β-d-thioglucopyranoside Chemical compound CCCCCCCCS[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O CGVLVOOFCGWBCS-RGDJUOJXSA-N 0.000 description 1
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- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 1
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- ZVVSSOQAYNYNPP-UHFFFAOYSA-N olaflur Chemical compound F.F.CCCCCCCCCCCCCCCCCCN(CCO)CCCN(CCO)CCO ZVVSSOQAYNYNPP-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
- B82B1/00—Nanostructures formed by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Definitions
- the present invention relates to pharmaceutically active compounds.
- the present invention particularly relates to ziprasidone, including nanoparticles of ziprasidone, especially nanoparticles comprising one or more surface stabilizers, and formulations comprising nanoparticles of ziprasidone.
- the present invention comprises a pharmaceutical formulation comprising: a compound selected from the group consisting of ziprasidone, having a maximum average particle size; a carrier; and optionally a surface stabilizer, for example at least two surface stabilizers.
- the present invention also comprises methods of treating psychosis with such a formulation and processes for making such a formulation.
- depot formulation which, inter alia, may be administered via intramuscular or subcutaneous injection.
- a depot formulation is specially formulated to provide slow absorption of the drug from the site of administration, often keeping therapeutic levels of the drug in the patient's system for days or weeks at a time.
- depot formulations comprising antipsychotic drugs can be useful in increasing patient compliance among schizophrenics.
- U.S. Patent No. 6,150, 366 (granted November 21 , 2000) describes a pharmaceutical composition describing crystalline ziprasidone and a carrier.
- U.S. Patent No. 6, 267, 989 (granted July 31 , 2001) describes a water- insoluble crystalline drug to which a surface modifier is adsorbed in an amount sufficient to maintain a defined particle size.
- WO 00/18374 (filed October 1, 1999) describes a controlled release nanoparticle composition.
- WO 00/09096 (filed August 12, 1999) describes an injectable nanoparticle formulation of naproxen. Accordingly, a need still exists for new drug therapies for the treatment of subjects suffering from or susceptible to psychosis - particularly, a long acting form of an atypical antipsychotic providing a suitable therapy that minimizes side effects while enhancing patient compliance through a reduced dosing regimen.
- ziprasidone is poorly soluble.
- the present invention relates to a pharmaceutical formulation comprising ziprasidone or a pharmaceutically acceptable salt thereof suitable for use as a depot formulation for administration via intramuscular or subcutaneous injection.
- the ziprasidone or ziprasidone salt in the formulation has a maximum average particle size.
- the invention comprises a pharmaceutical formulation comprising (1) a pharmaceutically acceptable amount of a compound selected from ziprasidone and a pharmaceutically acceptable salt of ziprasidone, which compound has a maximum average particle size, and (2) a pharmaceutically acceptable carrier.
- the formulation comprises (1) a pharmaceutically effective amount of a compound selected from the group ziprasidoneand a pharmaceutically acceptable salt thereof, which compound has a maximum average particle size; (2) a pharmaceutically acceptable carrier; and (3) at least one surface stabilizer.
- the formulation consists of at least two surface stabilizers.
- the formulations of the invention may, for example, comprise from one to ten surface stabilizers, preferably two to five stabilizers.
- the formulation consists of two -A-
- the formulation consists of two surface stabilizers and a bulking agent.
- the present invention comprises processes for preparing such a formulation.
- the present invention comprises the use of such a composition as a medicament in the treatment of psychosis, schizophrenia, schizoaffective disorders, non-schizophrenic psychoses, behavioral disturbances associated with neurodegenerative disorders, e.g. in dementia, behavioral disturbances in mental retardation and autism, Tourette's syndrome, bipolar disorder (for example bipolar mania, bipolar depression, or for effecting mood stabilization in bipolar disorder), depression and anxiety.
- the present invention comprises methods of treating psychosis, schizophrenia, schizoaffective disorders, non-schizophrenic psychoses, behavioral disturbances associated with neurodegenerative disorders, e.g. in dementia, behavioral disturbances in mental retardation and autism, Tourette's syndrome, bipolar disorder (for example bipolar mania, bipolar depression, or for effecting mood stabilization in bipolar disorder), depression and anxiety.
- the invention relates to nanoparticles of ziprasidone or nanoparticles of a pharmaceutically acceptable salt of ziprasidone.
- the nanoparticles of ziprasidone or nanoparticles of a pharmaceutically acceptable ziprasidone salt comprise a surface stabilizer.
- the nanoparticles of ziprasidone or nanoparticles of a pharmaceutically acceptable ziprasidone salt comprise at least two surface stabilizers.
- the term "compound” refers to a form of a therapeutic or diagnostic agent which is a component of an injectable depot formulation.
- the compound may be a pharmaceutical, including, without limitation, biologies such as proteins, peptides and nucleic acids or a diagnostic, including, without limitation, contrast agents.
- the compound is crystalline.
- the compound is amorphous.
- the compound is a mixture of crystalline and amorphous forms.
- the compound is ziprasidone.
- the compound is selected from the group
- ziprasidone free base and a pharmaceutically acceptable salt of ziprasidone.
- the ziprasidone may be crystalline, amorphous, or a mixture of crystalline and amorphous.
- the compound has low aqueous solubility.
- Ziprasidone is a poorly water soluble drug, i.e. it has low aqueous solubility.
- the logP of the compound is at least about 3 or greater.
- the compound has a high melting point. ' A high melting compound is one with a melting point greater than about 130 degrees Celsius.
- a first surface stabilizer is present in an amount sufficient to maintain an effective average particle size of the compound.
- one or more surface stabilizers are present in an amount sufficient to maintain an effective particle size of the compound.
- a surface stabilizer is a surfactant.
- a surface stabilizer is a crystallization inhibitor.
- surfactant refers to amphipathic molecules that consist of a non- polar hydrophobic portion, exemplified by a straight or branched hydrocarbon or fluorocarbon chain containing 8-18 carbon atoms, which is attached to a polar or ionic portion (hydrophilic).
- the hydrophilic portion may be nonionic, ionic or zwitterionic and accompanied by counter ions.
- surfactants anionic, cationic, amphoteric, nonionic and polymeric. In the case of nonionic and polymeric surfactants, a single surfactant may be properly classified as a member of both categories.
- An exemplary group of surfactants that may be properly classified in this manner are the ethylene oxide-propylene oxide copolymers, referred to as Pluronics® (Wyandotte), Synperonic PE ®(ICI) and Poloxamers® (BASF). Polymers such as HPMC and PVP are sometimes classified as polymeric surfactants.
- Exemplary classes of surfactants include, without limitation: carboxylates, sulphates, sulphonates, phosphates, sulphosuccinates, isethionates, taurates, quartemary ammonium compounds, N-alkyl betaines, N-alkyl amino propionates, alcohol ethoxylates, alkyl phenol ethoxylates, fatty acid ethoxylates, monoalkaolamide ethoxylates, sorbitan ester ethoxylates, fatty amine ethoxylates, ethylene oxide-propylene oxide co-polymers, glycerol esters, glycol esters, glucosides, sucrose esters, amino oxides, sulphinyl surfactants, polyoxyethylene allcyl ethers, polyoxyethylene alkyl ethers, polyglycolized glycerides, short-chain glyceryl mono-alkylates, alkyl ary
- ethylene oxide-propylene oxide copolymers refers to four types of nonionic block copolymers, of which Pluronic® F108 is one, as described in Table A-2, immediately below:
- Pluronic® F108 refers to poloxamer 338 and is the polyoxyethylene-polyoxypropylene block copolymer that conforms generally to the formula HO[CH 2 CH 2 O] n [CH(CH 3 )CH 2 O]JCH 2 CH 2 O] n H in which the average values of n, m and n are respectively 128, 54 and 128.
- crystallization inhibitor refers to a polymer or other substances that can substantially inhibit precipitation and/or crystallization of a poorly water- soluble drug.
- a polymeric surfactant is a crystallization inhibitor.
- the crystallization inhibitor is a cellulosic or non- cellulosic polymer and is substantially water-soluble.
- the crystallization inhibitor is HPMC.
- a crystallization inhibitor is polyvinylpyrrolidone (PVP).
- Table A-3 Method to Test Crystallization Inhibitors for Efficacy
- a technician performing Test I will readily find a suitable polymer concentration for the test within the polymer concentration range provided above, by routine experimentation.
- a concentration of the polymer is selected such that when Test I is performed, the apparent absorbance of the second sample solution is not greater than about 50% of the apparent absorbance of the first sample solution
- Isolated site hydrates are ones in which the water molecules are isolated from direct contact with each other by intervening organic molecules.
- channel hydrates the water molecules lie in lattice channels where they are next to other water molecules.
- metal-ion coordinated hydrates the water molecules are bonded to the metal ion.
- the compound is ziprasidone free base. In still another embodiment, the compound is ziprasidone mesylate. In another embodiment, the compound is ziprasidone mesylate trihydrate. In still another embodiment, the compound is ziprasidone HCI. In another embodiment of the compound, the compound is crystalline. In still another embodiment, the compound is crystalline ziprasidone free base. In still another embodiment, the compound is crystalline ziprasidone mesylate. In still another embodiment, the compound is crystalline ziprasidone HCi. In another embodiment of the injectable depot formulation, the pharmaceutically acceptable carrier is water.
- the nanoparticles have an average particle size of about 250 nm.
- the compound is crystalline ziprasidone free base and the average particle size is about 250 nm.
- the amount by weight of ziprasidone is from about
- the amount by weight is from about 20% by weight to about
- a first surface stabilizer is an anionic surfactant. In another embodiment, a first surface stabilizer is a cationic surfactant. In another embodiment, a first surface stabilizer is an amphoteric surfactant. In another embodiment, a first surface stabilizer is a non- ionic surfactant. In another embodiment, a first surface stabilizer is a polymeric surfactant.
- a first surface stabilizer is a crystallization inhibitor.
- the amount by weight of the third surface stabilizer is about 0.1 % by weight of the total volume of the formulation. In still another embodiment, the amount by weight of the third surface stabilizer is about 0.02% by weight of the total volume of the formulation. In still another embodiment, the amount by weight of the third surface stabilizer is about 0.5% by weight of the total volume of the formulation. In still another embodiment, the amount by weight of the third surface stabilizer is about 1.0% by weight of the total volume of the formulation.
- a third surface stabilizer is a surfactant.
- the third surface stabilizer is selected from the group consisting of Pluronic® F68, benzalkonium chloride, lecithin and SLS.
- a third surface stabilizer is Pluronic® F68.
- a third surface stabilizer is benzalkonium chloride.
- a third surface stabilizer is lecithin.
- a third surface stabilizer is SLS.
- the total amount by weight of surface stabilizers in a formulation is about 6% or less, more preferably about 5% or less.
- the compound nanoparticles can be made using several different methods, including, for example, milling, precipitation and high pressure homogenization. Exemplary methods of making compound nanoparticles are described in U.S. Patent No. 5,145, 684, the entire content of which is hereby incorporated by reference.
- the optimal effective average particle size of the invention can be obtained by controlling the process of particle size reduction, such as controlling the milling time and the amount of surface stabilizer added. Crystal growth and particle aggregation can also be minimized by milling or precipitating the composition under colder temperatures, and by storing the final composition at colder temperatures.
- the compound is milled in the presence of at least one surface stabilizer, more preferable in the presence of at least two stabilizers; or the compound is contacted with at least one, more preferably at least two surface stabilizers, subsequent to attrition.
- Other compounds such as a bulking agent, can be added to the compound/surface stabilizer mixture during the size reduction process.
- Dispersions can be manufactured continuously or in a batch mode.
- the resultant nanoparticulate drug dispersion can be utilized in solid or liquid dosage formulations.
- the nanoparticulate dispersion may be utilized in intramuscular depot formulations suitable for injection.
- Exemplary useful mills include low energy mills, such as a roller mill, attritor mill, vibratory mill and ball mill, and high energy mills, such as Dyno mills, Netzsch mills, DC mills, and Planetary mills.
- Media mills include sand ills and bead mills.
- the compound is placed into a reservoir along with a dispersion medium (for example, water) and at least two surface stabilizers.
- the mixture is recirculated through a chamber containing media and a rotating shaft/impeller.
- the rotating shaft agitates the media which subjects the compound to impacting and sheer forces, thereby reducing particle size. 2. Grinding Media
- Exemplary grinding media comprises particles that are substantially spherical in shape, such as beads, consisting essentially of polymeric resin.
- the grinding media comprises a core having a coating of a polymeric resin adhered thereon.
- Other examples of grinding media comprise essentially spherical particles comprising glass, metal oxide, or ceramic.
- the grinding media preferably ranges in size from about 10 ⁇ m to about 3 mm.
- exemplary grinding media is from about 20 ⁇ m to about 2 mm.
- exemplary grinding media is from about 30 ⁇ m to about 1 mm in size.
- the grinding media is about 500 ⁇ m in size.
- the polymeric resin can have a density from about 0.8 to about 3.0 g/ml.
- the grinding media is separated from the milled nanoparticulate compound using conventional separation techniques in a secondary process, including, without limitation, simple filtration, sieving through a mesh filter or screen, and the like. Other separation techniques such as centrifugation may also be employed.
- the formulation is preferably precipitated after addition to a solution of at least one, more preferably at least two, surface stabilizers.
- the method can be followed by removal of any formed salt, if present, by dialysis or diafiltration and concentration of the dispersion by conventional means.
- the resultant nanoparticulate drug dispersion can be utilized in solid or liquid dosage formulations. In another embodiment, the nanoparticulate dispersion may be utilized in intramuscular depot formulations suitable for injection.
- the conditions that can be treated in accordance with the present invention include psychosis, schizophrenia, schizoaffective disorders, non-schizophrenic psychoses, behavioral disturbances associated with neurodegenerative disorders, e.g. in dementia, behavioral disturbances in mental retardation and autism, Tourette's syndrome, bipolar disorder (for example bipolar mania, bipolar depression, or effecting mood stabilization in bipolar disorder), depression and anxiety.
- psychosis schizophrenia, schizoaffective disorders, non-schizophrenic psychoses
- behavioral disturbances associated with neurodegenerative disorders e.g. in dementia, behavioral disturbances in mental retardation and autism, Tourette's syndrome
- bipolar disorder for example bipolar mania, bipolar depression, or effecting mood stabilization in bipolar disorder
- depression and anxiety for example bipolar mania, bipolar depression and anxiety.
- a formulation described in this specification is administered in an amount effective to treat conditions listed herein.
- the depot formulations of the present invention are administered by injection, whether subcutaneously or intramuscularly, and in a dose effective for the treatment intended.
- Therapeutically effective doses of the compounds required to prevent or arrest the progress of or to treat the medical condition are readily ascertained by one of ordinary skill in the art using preclinical and clinical approaches familiar to the medicinal arts.
- a coarse suspension was prepared by placing 8.86 gm of ziprasidone free base in a 100 ml milling chamber with 48.90 gm of milling media (500 micron . polystyrene beads).
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Priority Applications (11)
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JP2008505990A JP2008538751A (ja) | 2005-04-13 | 2006-04-10 | ナノ粒子組成物を持続放出するための注射用デポ製剤および方法 |
US11/911,457 US20080193542A1 (en) | 2005-04-13 | 2006-04-10 | Injectable Deopot Formulations and Methods For Providing Sustained Release of Nanoparticle Compositions |
MX2007012103A MX2007012103A (es) | 2005-04-13 | 2006-04-10 | Formulaciones deposito inyectables y metodos para proporcionar una liberacion sostenida de composiciones de nanoparticulas. |
CA002605153A CA2605153A1 (en) | 2005-04-13 | 2006-04-10 | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
EP06744618A EP1874268A1 (en) | 2005-04-13 | 2006-04-10 | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
NZ561950A NZ561950A (en) | 2005-04-13 | 2006-04-10 | Injectable depot formulations comprising ziprasidone in nanoparticle form with two surface stabilizers |
AU2006233345A AU2006233345A1 (en) | 2005-04-13 | 2006-04-10 | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
BRPI0609299-3A BRPI0609299A2 (pt) | 2005-04-13 | 2006-04-10 | formulaÇÕes de depàsito injetÁveis e mÉtodos para proporcionar liberaÇço sustentada de composiÇÕes de nanopartÍculas |
IL186131A IL186131A0 (en) | 2005-04-13 | 2007-09-20 | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
US12/043,014 US20080305161A1 (en) | 2005-04-13 | 2008-03-05 | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
AU2010201801A AU2010201801A1 (en) | 2005-04-13 | 2010-05-05 | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
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US67112405P | 2005-04-13 | 2005-04-13 | |
US60/671,124 | 2005-04-13 |
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US12/043,014 Continuation-In-Part US20080305161A1 (en) | 2005-04-13 | 2008-03-05 | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
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PCT/IB2006/001094 WO2006109183A1 (en) | 2005-04-13 | 2006-04-10 | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
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US (1) | US20080193542A1 (es) |
EP (1) | EP1874268A1 (es) |
JP (1) | JP2008538751A (es) |
KR (1) | KR20070119678A (es) |
CN (1) | CN101166514A (es) |
AU (2) | AU2006233345A1 (es) |
BR (1) | BRPI0609299A2 (es) |
CA (1) | CA2605153A1 (es) |
IL (1) | IL186131A0 (es) |
MX (1) | MX2007012103A (es) |
NZ (1) | NZ561950A (es) |
RU (1) | RU2407529C2 (es) |
WO (1) | WO2006109183A1 (es) |
ZA (1) | ZA200708188B (es) |
Cited By (6)
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EP1901722A1 (en) * | 2005-06-20 | 2008-03-26 | Elan Pharma International Limited | Nanoparticulate and controlled release compositions comprising aryl-heterocyclic compounds |
US8951555B1 (en) | 2000-10-30 | 2015-02-10 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8975273B2 (en) | 1999-10-29 | 2015-03-10 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9469630B2 (en) | 2010-10-18 | 2016-10-18 | Sumitomo Dainippon Pharma Co., Ltd. | Sustained-release formulation for injection |
US10166231B2 (en) | 2011-04-15 | 2019-01-01 | Janssen Pharmaceutica Nv | Freeze dried drug nanosuspensions |
US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
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KR20090080143A (ko) * | 2003-09-02 | 2009-07-23 | 화이자 프로덕츠 인크. | 지프라시돈의 지속 방출형 투여 형태 |
US20080305161A1 (en) * | 2005-04-13 | 2008-12-11 | Pfizer Inc | Injectable depot formulations and methods for providing sustained release of nanoparticle compositions |
CN101242813A (zh) * | 2005-06-20 | 2008-08-13 | 依兰药物国际有限公司 | 包含芳基-杂环化合物的毫微粒和控制释放组合物 |
ES2437331T3 (es) * | 2007-07-12 | 2014-01-10 | Janssen R&D Ireland | Forma cristalina de 4-[[4-[[4-(2-cianoetenil)-2,6-dimetilfenil]amino]-2-pirimidinil]amino]benzonitrilo |
CN104814926A (zh) * | 2015-04-08 | 2015-08-05 | 中国药科大学 | 一种鲁拉西酮纳米混悬剂及其制备方法 |
ES2960753T3 (es) * | 2015-09-21 | 2024-03-06 | Teva Pharmaceuticals Int Gmbh | Formulaciones de olanzapina de liberación sostenida |
WO2018172850A1 (en) | 2017-03-20 | 2018-09-27 | Teva Pharmaceuticals International Gmbh | Sustained release olanzapine formulaitons |
CN109998991A (zh) * | 2019-04-28 | 2019-07-12 | 中国药科大学 | 一种盐酸鲁拉西酮长效肌肉注射纳米混悬液及其制备方法 |
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-
2006
- 2006-04-10 AU AU2006233345A patent/AU2006233345A1/en not_active Abandoned
- 2006-04-10 JP JP2008505990A patent/JP2008538751A/ja not_active Withdrawn
- 2006-04-10 RU RU2007137846/15A patent/RU2407529C2/ru not_active IP Right Cessation
- 2006-04-10 CN CNA2006800144209A patent/CN101166514A/zh active Pending
- 2006-04-10 US US11/911,457 patent/US20080193542A1/en not_active Abandoned
- 2006-04-10 CA CA002605153A patent/CA2605153A1/en not_active Abandoned
- 2006-04-10 WO PCT/IB2006/001094 patent/WO2006109183A1/en active Application Filing
- 2006-04-10 BR BRPI0609299-3A patent/BRPI0609299A2/pt not_active IP Right Cessation
- 2006-04-10 KR KR1020077023308A patent/KR20070119678A/ko active IP Right Grant
- 2006-04-10 EP EP06744618A patent/EP1874268A1/en not_active Withdrawn
- 2006-04-10 MX MX2007012103A patent/MX2007012103A/es not_active Application Discontinuation
- 2006-04-10 NZ NZ561950A patent/NZ561950A/en not_active IP Right Cessation
-
2007
- 2007-09-20 IL IL186131A patent/IL186131A0/en unknown
- 2007-09-25 ZA ZA200708188A patent/ZA200708188B/xx unknown
-
2010
- 2010-05-05 AU AU2010201801A patent/AU2010201801A1/en not_active Abandoned
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WO2004037289A2 (en) * | 2002-10-25 | 2004-05-06 | Pfizer Products Inc. | Novel injectable depot formulations |
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WO2005020929A2 (en) * | 2003-09-02 | 2005-03-10 | Imran Ahmed | Sustained release dosage forms of ziprasidone |
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US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US10076516B2 (en) | 1999-10-29 | 2018-09-18 | Purdue Pharma L.P. | Methods of manufacturing oral dosage forms |
US8975273B2 (en) | 1999-10-29 | 2015-03-10 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US8980291B2 (en) | 1999-10-29 | 2015-03-17 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9675611B1 (en) | 1999-10-29 | 2017-06-13 | Purdue Pharma L.P. | Methods of providing analgesia |
US9669024B2 (en) | 1999-10-29 | 2017-06-06 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9056107B1 (en) | 1999-10-29 | 2015-06-16 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
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US9320717B2 (en) | 1999-10-29 | 2016-04-26 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9060940B2 (en) | 2000-10-30 | 2015-06-23 | Purdue Pharma L.P. | Controlled release hydrocodone |
US9669023B2 (en) | 2000-10-30 | 2017-06-06 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
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US9289391B2 (en) | 2000-10-30 | 2016-03-22 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
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US8951555B1 (en) | 2000-10-30 | 2015-02-10 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9504681B2 (en) | 2000-10-30 | 2016-11-29 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9517236B2 (en) | 2000-10-30 | 2016-12-13 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9526724B2 (en) | 2000-10-30 | 2016-12-27 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9572804B2 (en) | 2000-10-30 | 2017-02-21 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9572805B2 (en) | 2000-10-30 | 2017-02-21 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9205056B2 (en) | 2000-10-30 | 2015-12-08 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US10022368B2 (en) | 2000-10-30 | 2018-07-17 | Purdue Pharma L.P. | Methods of manufacturing oral formulations |
US9056052B1 (en) | 2000-10-30 | 2015-06-16 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9023401B1 (en) | 2000-10-30 | 2015-05-05 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US9682077B2 (en) | 2000-10-30 | 2017-06-20 | Purdue Pharma L.P. | Methods of providing analgesia |
EP1901722A1 (en) * | 2005-06-20 | 2008-03-26 | Elan Pharma International Limited | Nanoparticulate and controlled release compositions comprising aryl-heterocyclic compounds |
EP1901722A4 (en) * | 2005-06-20 | 2011-06-15 | Elan Pharma Int Ltd | NANOTEHOUS COMPOSITIONS WITH CONTROLLED RELEASE FROM ARYL-HETEROCYCLIC COMPOUNDS |
US9469630B2 (en) | 2010-10-18 | 2016-10-18 | Sumitomo Dainippon Pharma Co., Ltd. | Sustained-release formulation for injection |
US10166231B2 (en) | 2011-04-15 | 2019-01-01 | Janssen Pharmaceutica Nv | Freeze dried drug nanosuspensions |
US11389448B2 (en) | 2011-04-15 | 2022-07-19 | Janssen Pharmaceutica Nv | Freeze dried drug nanosuspensions |
US11819502B2 (en) | 2011-04-15 | 2023-11-21 | Janssen Pharmaceutica Nv | Freeze dried drug nanosuspensions |
Also Published As
Publication number | Publication date |
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MX2007012103A (es) | 2007-11-20 |
RU2407529C2 (ru) | 2010-12-27 |
EP1874268A1 (en) | 2008-01-09 |
IL186131A0 (en) | 2008-01-20 |
US20080193542A1 (en) | 2008-08-14 |
AU2010201801A1 (en) | 2010-05-27 |
CN101166514A (zh) | 2008-04-23 |
KR20070119678A (ko) | 2007-12-20 |
CA2605153A1 (en) | 2006-10-19 |
AU2006233345A1 (en) | 2006-10-19 |
NZ561950A (en) | 2010-09-30 |
JP2008538751A (ja) | 2008-11-06 |
RU2007137846A (ru) | 2009-06-20 |
BRPI0609299A2 (pt) | 2010-03-23 |
ZA200708188B (en) | 2008-10-29 |
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